Chapter 11. Protein Data Bank

The success of the Human Genome Project in decoding the DNA sequence of human genes has captured the public imagination, but another project has been quietly gaining momentum, and it promises equally revolutionary results. This project is an international effort to determine the 3D structure of a comprehensive range of proteins on a genome-wide level using high-throughput analytical technologies. This international effort is the foundation of the new field of structural genomics.

Recent and expected advances in technology promise an accelerating pace of protein structure determination. The storehouse for all of this data is the Protein Data Bank (PDB). The PDB may be found on the web at http://www.rcsb.org/pdb/.

Finding the amino acid or primary sequence is just the beginning of studying a protein. Proteins fold locally into secondary structures such as alpha helices, beta-strands, and turns. Two or three adjacent secondary structures might combine into common local folds called " motifs" or "supersecondary" structures such as beta sheets or alpha-alpha units. These building blocks then fold into the 3D or tertiary structure of a protein. Finally, one or more tertiary structures may be combined as subunits into a quaternary structure such as an enzyme or a virus.

Without knowing how a protein folds into a 3D structure, you are less likely to know what the protein does or how it does it. Even if you know that the protein is implicated in a disease, knowledge of its tertiary structure is usually needed to find a possible treatment. Knowing the tertiary conformation of the active site of a protein (which may involve amino acids that are far apart in terms of the primary sequence but which are brought together by the folding of the protein) is critical to guide the selection of targets for new drugs.

Now that the basic genetic information of a number of organisms, including humans, has been decoded, a primary challenge facing biologists is to learn as much as possible about the proteins those genes produce and how they interact.

In fact, one of the great questions of modern biology is how the primary amino acid sequence of a protein determines its ultimate 3D shape. If a computational method can be found to reliably predict the fold of a protein from its amino acid sequence, the effect on biology and medicine would be profound.

In this chapter, you'll learn the basics of PDB files and how to parse out selected information form them. You'll also explore interesting Perl techniques for finding and iterating over lots of files, as well as controlling other bioinformatics programs from a Perl program. The exercises at the end of the chapter challenge you to extend the introductory material presented here to gain access to more of the PDB data.